Long non-coding RNAs and VEGF in ovarian cancer: mechanisms and therapeutic potential

Epithelial ovarian cancer (EOC) remains the most lethal gynecological malignancy globally, primarily due to its late-stage diagnosis and the rapid development of therapeutic resistance. This comprehensive review synthesizes the intricate roles of long non-coding RNAs (lncRNAs) and Vascular Endothelial Growth Factor (VEGF) in the pathogenesis and progression of ovarian cancer, highlighting their underlying molecular mechanisms and emerging therapeutic implications. LncRNAs, a diverse class of non-protein-coding transcripts, exert profound regulatory control over gene expression at transcriptional, post-transcriptional, and epigenetic levels, acting as both oncogenes and tumor suppressors in EOC. Concurrently, VEGF, a pivotal cytokine, is a master regulator of angiogenesis, fostering tumor growth, metastasis, and the characteristic malignant ascites in EOC. Recent research has unveiled complex regulatory networks, and this review specifically synthesizes the evidence for hypoxia-driven positive feedback loops and regulation within the unique peritoneal tumor microenvironment. In these contexts, lncRNAs intricately modulate VEGF expression and signaling, often through hypoxia-inducible factors (HIFs) and microRNA (miRNA) sponging, thereby locking in aggressive angiogenic and chemoresistant phenotypes. While anti-VEGF therapies have shown clinical benefit, their efficacy is often limited by acquired resistance. This review explores the potential of targeting specific lncRNAs, either alone or in combination with anti-VEGF agents, as a promising strategy to overcome resistance and enhance personalized medicine in EOC. The discussion includes preclinical advancements in lncRNA-based therapeutics and underscores the critical need for continued research to translate these findings into effective clinical interventions.